Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury
Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2(+)-GFP(+)-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GF...
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| description | Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2(+)-GFP(+)-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2(+)-GFP(+)-OPCs and transplanted them into the rats' cervical 4-5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2(+)-GFP(+)-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2(+)-GFP(+)-OPCs primarily differentiated into adenomatous polyposis coli (APC(+)) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2(+)-GFP(+)-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2(+)-GFP(+)-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS). |
| doi_str_mv | 10.1371/journal.pone.0057534 |
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One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2(+)-GFP(+)-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2(+)-GFP(+)-OPCs and transplanted them into the rats' cervical 4-5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2(+)-GFP(+)-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2(+)-GFP(+)-OPCs primarily differentiated into adenomatous polyposis coli (APC(+)) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2(+)-GFP(+)-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2(+)-GFP(+)-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS).</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0057534</identifier><identifier>PMID: 23460872</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenomatous polyposis coli ; Animals ; Axons - pathology ; Axons - ultrastructure ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biology ; Cancer ; Cell Differentiation ; Cell Lineage ; Cell Movement ; Cell Shape ; Cell Survival ; Central nervous system ; Demyelinating Diseases - complications ; Demyelinating Diseases - physiopathology ; Demyelinating Diseases - therapy ; Demyelination ; Electron microscopy ; Embryo cells ; Embryology ; Female ; Forelimb - physiopathology ; Gene expression ; Glial stem cells ; Grafts ; Green Fluorescent Proteins - metabolism ; Histology ; Immunofluorescence ; Injuries ; Injury analysis ; Irradiation ; Laboratory animals ; Lesions ; Locomotion ; Locomotion - physiology ; Medicine ; Mice ; Multiple sclerosis ; Myelin ; Myelination ; Nerve Tissue Proteins - metabolism ; Olig2 protein ; Oligodendrocyte Transcription Factor 2 ; Oligodendrocytes ; Oligodendroglia - cytology ; Oligodendroglia - transplantation ; Polyposis coli ; Precursors ; Radiation ; Radiation Injuries - complications ; Radiation Injuries - physiopathology ; Radiation Injuries - therapy ; Radiation therapy ; Rats ; Rats, Wistar ; Recovery ; Recovery of function ; Rodents ; Spinal Cord - pathology ; Spinal Cord - radiation effects ; Spinal cord injuries ; Spinal Cord Injuries - complications ; Spinal Cord Injuries - physiopathology ; Spinal Cord Injuries - therapy ; Stem Cell Transplantation ; Stem cells ; Stem Cells - cytology ; Transplantation</subject><ispartof>PloS one, 2013-02, Vol.8 (2), p.e57534</ispartof><rights>2013 Sun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Sun et al 2013 Sun et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-aa19cb135af76f6c86023fbeb10374b3f5ff96db480dbc8b02a26e0a6129718b3</citedby><cites>FETCH-LOGICAL-c526t-aa19cb135af76f6c86023fbeb10374b3f5ff96db480dbc8b02a26e0a6129718b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583877/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583877/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23864,27922,27923,53789,53791,79370,79371</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23460872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Nait-Oumesmar, Brahim</contributor><creatorcontrib>Sun, Yan</creatorcontrib><creatorcontrib>Xu, Chong-Chong</creatorcontrib><creatorcontrib>Li, Jin</creatorcontrib><creatorcontrib>Guan, Xi-Yin</creatorcontrib><creatorcontrib>Gao, Lu</creatorcontrib><creatorcontrib>Ma, Li-Xiang</creatorcontrib><creatorcontrib>Li, Rui-Xi</creatorcontrib><creatorcontrib>Peng, Yu-Wen</creatorcontrib><creatorcontrib>Zhu, Guo-Pei</creatorcontrib><title>Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2(+)-GFP(+)-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2(+)-GFP(+)-OPCs and transplanted them into the rats' cervical 4-5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2(+)-GFP(+)-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2(+)-GFP(+)-OPCs primarily differentiated into adenomatous polyposis coli (APC(+)) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2(+)-GFP(+)-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2(+)-GFP(+)-OPCs. 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metabolism</subject><subject>Histology</subject><subject>Immunofluorescence</subject><subject>Injuries</subject><subject>Injury analysis</subject><subject>Irradiation</subject><subject>Laboratory animals</subject><subject>Lesions</subject><subject>Locomotion</subject><subject>Locomotion - physiology</subject><subject>Medicine</subject><subject>Mice</subject><subject>Multiple sclerosis</subject><subject>Myelin</subject><subject>Myelination</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Olig2 protein</subject><subject>Oligodendrocyte Transcription Factor 2</subject><subject>Oligodendrocytes</subject><subject>Oligodendroglia - cytology</subject><subject>Oligodendroglia - transplantation</subject><subject>Polyposis coli</subject><subject>Precursors</subject><subject>Radiation</subject><subject>Radiation Injuries - complications</subject><subject>Radiation Injuries - physiopathology</subject><subject>Radiation Injuries - therapy</subject><subject>Radiation therapy</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Recovery</subject><subject>Recovery of function</subject><subject>Rodents</subject><subject>Spinal Cord - pathology</subject><subject>Spinal Cord - radiation effects</subject><subject>Spinal cord injuries</subject><subject>Spinal Cord Injuries - complications</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal Cord Injuries - therapy</subject><subject>Stem Cell Transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Transplantation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1UltrFDEUHkSxtfoPRAM-75rL5DIvghRbCwVf6nNIMsk2SzYZT2ZaFv-8s91paR98OiHnu3H4muYjwWvCJPm6LRNkk9ZDyX6NMZecta-aU9IxuhIUs9fP3ifNu1q3M4gpId42J5S1AitJT5u_N2ByHZLJoxljyagEVFLclN7nHorbjx4N4N0EtQByPqWK4m6AcucrSsWVXXmg9T5EF8d5mRGYed7H8RbVIc4RkSvQowhg-ng0iXk7wf598yaYVP2HZZ41vy9-3Jz_XF3_urw6_369cpyKcWUM6ZwljJsgRRBOCUxZsN4SzGRrWeAhdKK3rcK9dcpiaqjw2AhCO0mUZWfN56PukErVy92qJoxhpajgckZcHRF9MVs9QNwZ2Otion74KLDRBsboktesDYR67rhsZcudsZ7S0AahcGeDwmrW-ra4TXbne-fzCCa9EH25yfFWb8qdZlwxJQ9hviwCUP5Mvo7_idweUQ5KreDDkwPB-lCQR5Y-FEQvBZlpn56neyI9NoL9A-iSvd0</recordid><startdate>20130227</startdate><enddate>20130227</enddate><creator>Sun, Yan</creator><creator>Xu, Chong-Chong</creator><creator>Li, Jin</creator><creator>Guan, Xi-Yin</creator><creator>Gao, Lu</creator><creator>Ma, Li-Xiang</creator><creator>Li, Rui-Xi</creator><creator>Peng, Yu-Wen</creator><creator>Zhu, Guo-Pei</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130227</creationdate><title>Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury</title><author>Sun, Yan ; Xu, Chong-Chong ; Li, Jin ; Guan, Xi-Yin ; Gao, Lu ; Ma, Li-Xiang ; Li, Rui-Xi ; Peng, Yu-Wen ; Zhu, Guo-Pei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-aa19cb135af76f6c86023fbeb10374b3f5ff96db480dbc8b02a26e0a6129718b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adenomatous polyposis coli</topic><topic>Animals</topic><topic>Axons - pathology</topic><topic>Axons - ultrastructure</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Biology</topic><topic>Cancer</topic><topic>Cell Differentiation</topic><topic>Cell Lineage</topic><topic>Cell Movement</topic><topic>Cell Shape</topic><topic>Cell Survival</topic><topic>Central nervous system</topic><topic>Demyelinating Diseases - complications</topic><topic>Demyelinating Diseases - physiopathology</topic><topic>Demyelinating Diseases - therapy</topic><topic>Demyelination</topic><topic>Electron microscopy</topic><topic>Embryo cells</topic><topic>Embryology</topic><topic>Female</topic><topic>Forelimb - physiopathology</topic><topic>Gene expression</topic><topic>Glial stem cells</topic><topic>Grafts</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Histology</topic><topic>Immunofluorescence</topic><topic>Injuries</topic><topic>Injury analysis</topic><topic>Irradiation</topic><topic>Laboratory animals</topic><topic>Lesions</topic><topic>Locomotion</topic><topic>Locomotion - 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One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2(+)-GFP(+)-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2(+)-GFP(+)-OPCs and transplanted them into the rats' cervical 4-5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2(+)-GFP(+)-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2(+)-GFP(+)-OPCs primarily differentiated into adenomatous polyposis coli (APC(+)) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2(+)-GFP(+)-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2(+)-GFP(+)-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS).</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23460872</pmid><doi>10.1371/journal.pone.0057534</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1330882657 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenomatous polyposis coli Animals Axons - pathology Axons - ultrastructure Basic Helix-Loop-Helix Transcription Factors - metabolism Biology Cancer Cell Differentiation Cell Lineage Cell Movement Cell Shape Cell Survival Central nervous system Demyelinating Diseases - complications Demyelinating Diseases - physiopathology Demyelinating Diseases - therapy Demyelination Electron microscopy Embryo cells Embryology Female Forelimb - physiopathology Gene expression Glial stem cells Grafts Green Fluorescent Proteins - metabolism Histology Immunofluorescence Injuries Injury analysis Irradiation Laboratory animals Lesions Locomotion Locomotion - physiology Medicine Mice Multiple sclerosis Myelin Myelination Nerve Tissue Proteins - metabolism Olig2 protein Oligodendrocyte Transcription Factor 2 Oligodendrocytes Oligodendroglia - cytology Oligodendroglia - transplantation Polyposis coli Precursors Radiation Radiation Injuries - complications Radiation Injuries - physiopathology Radiation Injuries - therapy Radiation therapy Rats Rats, Wistar Recovery Recovery of function Rodents Spinal Cord - pathology Spinal Cord - radiation effects Spinal cord injuries Spinal Cord Injuries - complications Spinal Cord Injuries - physiopathology Spinal Cord Injuries - therapy Stem Cell Transplantation Stem cells Stem Cells - cytology Transplantation |
| title | Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T06%3A10%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transplantation%20of%20oligodendrocyte%20precursor%20cells%20improves%20locomotion%20deficits%20in%20rats%20with%20spinal%20cord%20irradiation%20injury&rft.jtitle=PloS%20one&rft.au=Sun,%20Yan&rft.date=2013-02-27&rft.volume=8&rft.issue=2&rft.spage=e57534&rft.pages=e57534-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0057534&rft_dat=%3Cproquest_plos_%3E2949769181%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1330882657&rft_id=info:pmid/23460872&rft_doaj_id=oai_doaj_org_article_34f12e5c574745cabe22f4f6809bf808&rfr_iscdi=true |